Journal of Biomolecular Structure & Dynamics最新文献_第6页

Identification of high-affinity pyridoxal kinase inhibitors targeting cancer therapy: an integrated docking and molecular dynamics simulation approach. 鉴定针对癌症治疗的高亲和力吡哆醛激酶抑制剂：一种综合对接和分子动力学模拟方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-14 DOI: 10.1080/07391102.2023.2246580

Pallabi Banerjee, Anshuman Chandra, Taj Mohammad, Nagendra Singh, Md Imtaiyaz Hassan, Imteyaz Qamar

{"title":"Identification of high-affinity pyridoxal kinase inhibitors targeting cancer therapy: an integrated docking and molecular dynamics simulation approach.","authors":"Pallabi Banerjee, Anshuman Chandra, Taj Mohammad, Nagendra Singh, Md Imtaiyaz Hassan, Imteyaz Qamar","doi":"10.1080/07391102.2023.2246580","DOIUrl":"10.1080/07391102.2023.2246580","url":null,"abstract":"Pyridoxal kinase (PDXK) is a vitamin B6-dependent transferase enzyme encoded by the PDXK gene, crucial for leukemic cell proliferation. Disruption of its activity causes altered metabolism and reduced levels of nucleotides and polyamines. PDXK and pyridoxal 5'-phosphate (PLP) are overexpressed in various carcinomas, making them promising targets for drug design against cancer. Targeting PDXK may hold promise as a therapeutic approach for cancer treatment. This study focused on discovering potential inhibitors that could selectively interrupt the binding of pyridoxal phosphate (PLP) to pyridoxal kinase (PDXK). A commercially available library of 7,28,747 natural and druglike compounds was virtually screened using a molecular docking approach to target the substrate binding pocket of PDXK. Six promising inhibitors were identified, and all-atom molecular dynamics simulations were conducted on the PDXK-ligand complexes for 100 ns to assess their binding conformational stability. The simulation results indicated that the binding of ZINC095099376, ZINC01612996, ZINC049841390, ZINC095098959, ZINC01482077, and ZINC03830976 induced a slight structural change and stabilized the PDXK structure. This analysis provided valuable information about the critical residues involved in the PDXK-PLP complex formation and can be utilized in designing specific and effective PDXK inhibitors. According to this study, these compounds could be developed as anticancer agents targeting PDXK as a potential candidate for further study.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-spectroscopic, calorimetric and molecular dynamics evaluation on non-classical intercalation of antiviral drug Molnupiravir with DNA. 对抗病毒药物莫能吡韦与 DNA 的非经典插层作用进行多光谱、量热和分子动力学评估。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-25 DOI: 10.1080/07391102.2023.2249994

K Pavithra, R Durga Priyadharshini, K N Vennila, Kuppanagounder P Elango

{"title":"Multi-spectroscopic, calorimetric and molecular dynamics evaluation on non-classical intercalation of antiviral drug Molnupiravir with DNA.","authors":"K Pavithra, R Durga Priyadharshini, K N Vennila, Kuppanagounder P Elango","doi":"10.1080/07391102.2023.2249994","DOIUrl":"10.1080/07391102.2023.2249994","url":null,"abstract":"The interaction of an antiviral drug Molnupiravir (MOL) with calf thymus DNA (CT-DNA) was investigated using a series of biophysical techniques. A significant hyperchromism with a blue shift nm in the UV-Vis spectra indicated a high binding affinity of MOL for CT-DNA with binding constants in the order of 105 M-1. Competitive fluorescent dye displacement assays with ethidium bromide (EB) and Hoechst 33258 suggested an intercalative mode of binding of MOL with CT-DNA. Thermodynamic profiles determined using fluorescence titration and isothermal titration calorimetric (ITC) analysis matched well with each other. The negative free energy change revealed that the MOL/CT-DNA complexation is a spontaneous process. The negative values of enthalpy and entropy changes indicated that H-bonding and van der Walls interactions play dominant roles in stabilizing the complex. A decrease in viscosity of CT-DNA solution upon adding MOL indicated a partial intercalation mode of binding which was well supported by circular dichroism (CD) spectral and effect of KI and denaturation studies. Molecular docking and metadynamics simulation studies clearly showed the partial intercalation of the pyrimidine ring of MOL into the base pairs of DNA. Free energy surface (FES) contour indicated that the drug/DNA complex is stabilized by H-bonding and pi-pi/pi-cation interactions.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10064979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational assessment of lipid facilitated membrane permeation of vancomycin using force-probe molecular dynamic simulation. 利用测力探针分子动力学模拟对万古霉素的脂质促进膜渗透进行计算评估。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-22 DOI: 10.1080/07391102.2023.2248513

Mohabbat Ansari, Sajad Moradi, Simzar Hosseinzadeh, Mohsen Shahlaei

{"title":"Computational assessment of lipid facilitated membrane permeation of vancomycin using force-probe molecular dynamic simulation.","authors":"Mohabbat Ansari, Sajad Moradi, Simzar Hosseinzadeh, Mohsen Shahlaei","doi":"10.1080/07391102.2023.2248513","DOIUrl":"10.1080/07391102.2023.2248513","url":null,"abstract":"In this study the efficacy of different edible lipids for drug permeation enhancement of vancomycin through biological membrane was investigated using molecular dynamic simulation. In this regard, at first the ability of the lipids for complex formation with the drug was evaluated for number of most common edible lipids including tripalmitin (TPA), trimyristin (TMY), labrafil (LAB), glycerol monostearate (GMS), glycerol monooleate (GMO), Distearoylphosphorylethanolamine (DSPE), dipalmitoylphosphatidylethanolamine (DPPE), Dipalmitoylphosphatidylcholine (DPPC), cholesterol (CL), stearic acid (SA), palmitic acid (PA) and oleic acid (OA). Then the complexes were pulled thorough a bilayer membrane while the changes in force were probed. The results showed that besides the SA, PA and OA the other examined lipids were able to perform a perfect molecular complex with the drug. Also the results of pulling simulation revealed that the least of force was needed for drug transmittance through the membrane when it was covered by LAB, TMY and DSPE. These results indicated that these lipids can be the excellent materials of choice as permeation enhancer for preparing a proper oral formulation of vancomycin.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phytochemical profiling and evaluation of the antidiabetic potential of Ichnocarpus frutescens (Krishna Sariva): kinetic study, molecular modelling, and free energy approach. Ichnocarpus frutescens (Krishna Sariva) 的植物化学成分分析和抗糖尿病潜力评估：动力学研究、分子建模和自由能方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-24 DOI: 10.1080/07391102.2023.2248265

Sonali Kumari, Ravi Saini, Abha Mishra

{"title":"Phytochemical profiling and evaluation of the antidiabetic potential of Ichnocarpus frutescens (Krishna Sariva): kinetic study, molecular modelling, and free energy approach.","authors":"Sonali Kumari, Ravi Saini, Abha Mishra","doi":"10.1080/07391102.2023.2248265","DOIUrl":"10.1080/07391102.2023.2248265","url":null,"abstract":"This research explored novel antidiabetic drugs from natural sources using the Ayurvedic Rasayana herb Ichnocarpus frutescens through invitro enzyme assay, kinetics study, and computational approaches. Invitro enzyme inhibition assay demonstrated the promising inhibitory activity of root extract against alpha-amylase (α-A) and alpha-glucosidase (α-G) enzyme with IC50 value 7.34 ± 0.22 mg/ml and 4.40 ± 0.25 mg/ml respectively. Enzyme kinetic study revealed the competitive inhibition of both proteins by Ichnocarpus frutescens extract. High-Resolution Liquid Chromatography Mass Spectrometer and Docking study revealed the better binding energy of phytoconstituents 23-Acetoxysoladulcidine, Atrovirinone, Bismurrayaquinone A, Lamprolobine, Zygadenine, and Gambiriin A3 than standard drug acarbose. Molecular modelling showed stable protein-ligands binding interaction during the 100 ns simulation. It revealed comparable Root Mean Square Deviation, Radius of Gyration, and Solvent Accessible Surface Area of these compounds with acarbose. The active site residues of both proteins remained stable and showed significantly less Root Mean Square Fluctuation. Molecular Mechanics with Generalised Bonn Surface Area analysis has illustrated the similar inhibitory activity of Zygadenine for α-A, 23-Acetoxysoladulcidine, and Gambiriin A3 for α-G protein, compared to the FDA-approved drug acarbose. Thus, the study suggested that the root of Ichnocarpus frutescens can be used as α-A and α-G inhibitors and be considered a compelling lead for the medication of type 2 diabetes.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-based virtual screening of natural compounds against wild and mutant (R1155K, A1156T and D1168A) NS3-4A protease of Hepatitis C virus. 针对丙型肝炎病毒野生和突变体（R1155K、A1156T 和 D1168A）NS3-4A 蛋白酶的基于结构的天然化合物虚拟筛选。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-30 DOI: 10.1080/07391102.2023.2246583

Mahesh Samantaray, Ramya Pattabiraman, T P Krishna Murthy, Amutha Ramaswamy, Manikanta Murahari, Swati Krishna, S Birendra Kumar

{"title":"Structure-based virtual screening of natural compounds against wild and mutant (R1155K, A1156T and D1168A) NS3-4A protease of Hepatitis C virus.","authors":"Mahesh Samantaray, Ramya Pattabiraman, T P Krishna Murthy, Amutha Ramaswamy, Manikanta Murahari, Swati Krishna, S Birendra Kumar","doi":"10.1080/07391102.2023.2246583","DOIUrl":"10.1080/07391102.2023.2246583","url":null,"abstract":"NS3-4A, a serine protease, is a primary target for drug development against Hepatitis C Virus (HCV). However, the effectiveness of potent next-generation protease inhibitors is limited by the emergence of mutations and resulting drug resistance. To address this, in this study a structure-based drug design approach is employed to screen a large library of 7320 natural compounds against both wild-type and mutant variants of NS3-4A protease. Telaprevir, a widely used protease inhibitor, was recruited as the control drug. The top 10 compounds with favorable binding affinities underwent drug-likeness evaluation. Based on ADMET studies, complexes of NP_024762 and NP_006776 were selected for molecular dynamic simulations. Principal component analysis (PCA) was employed to explore the conformational space and protein dynamics of the protein-ligand complex using a Free Energy Landscape (FEL) approach. The cosine values obtained from FEL analysis ranged from 0 to 1, and eigenvectors with cosine values below 0.2 were chosen for further analysis. To forecast binding free energies and evaluate energy contributions per residue, the MM-PBSA method was employed. The results highlighted the crucial role of amino acids in the catalytic domain for the binding of the protease with phytochemicals. Stable associations between the top compounds and the target protease were confirmed by the formation of hydrogen bonds in the binding pocket involving residues: His1057, Gly1137, Ser1139, and Ala1157. These findings suggest the potential of these compounds for further validation through biological evaluation.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10115773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Theoretical insights into the binding interaction of Nirmatrelvir with SARS-CoV-2 Mpro mutants (C145A and C145S): MD simulations and binding free-energy calculation to understand drug resistance. Nirmatrelvir与SARS-CoV-2 Mpro突变体（C145A和C145S）结合相互作用的理论见解：通过 MD 模拟和结合自由能计算了解耐药性。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-20 DOI: 10.1080/07391102.2023.2248519

Priyanka Purohit, Madhusmita Panda, Jules Tshishimbi Muya, Pradipta Bandyopadhyay, Biswa Ranjan Meher

{"title":"Theoretical insights into the binding interaction of Nirmatrelvir with SARS-CoV-2 Mpro mutants (C145A and C145S): MD simulations and binding free-energy calculation to understand drug resistance.","authors":"Priyanka Purohit, Madhusmita Panda, Jules Tshishimbi Muya, Pradipta Bandyopadhyay, Biswa Ranjan Meher","doi":"10.1080/07391102.2023.2248519","DOIUrl":"10.1080/07391102.2023.2248519","url":null,"abstract":"Mpro, the main protease and a crucial enzyme in SARS-CoV-2 is the most fascinating molecular target for pharmacological treatment and is also liable for viral protein maturation. For antiviral therapy, no drugs have been approved clinically to date. Targeting the Mpro with a compound having inhibitory properties against it can hinder viral replication. The therapeutic potential of the antiviral compound Nirmatrelvir (NMV) against SARS-CoV-2 Mpro was investigated using a systematic approach of molecular docking, MD simulations, and binding free energy calculation based on the MM-GBSA method. NMV, a covalent inhibitor with a recently revealed chemical structure, is a promising oral antiviral clinical candidate with significant in vitro anti-SARS-CoV-2 action in third-phase clinical trials. To explore the therapeutic ability and possible drug resistance, the Mpro system was studied for WT and two of its primary mutants (C145A & C145S). The protein-ligand (Mpro/NMV) complexes were further examined through long MD simulations to check the possible drug resistance in the mutants. To understand the binding affinity, the MM-GBSA method was applied to the Mpro/NMV complexes. Moreover, PCA analysis confirms the detachment of the linker region from the major domains in C145S and C145A mutants allowing for conformational alterations in the active-site region. Based on the predicted biological activities and binding affinities of NMV to WT and mutant (C145A & C145S) Mpro, it can be stipulated that NMV may have conventional potency to act as an anti-viral agent against WT Mpro, while the catalytic-dyad mutations may show substantial mutation-induced drug resistance.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10022435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of potential Escherichia coli DNA gyrase B inhibitors targeting antibacterial therapy: an integrated docking and molecular dynamics simulation study. 以抗菌治疗为目标的潜在大肠杆菌 DNA 回旋酶 B 抑制剂的鉴定：一项综合对接和分子动力学模拟研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-22 DOI: 10.1080/07391102.2023.2249117

Bader S Alotaibi, Mohammed Ageeli Hakami, Talha Jawaid, Nawaf Alshammari, Reem Binsuwaidan, Mohd Adnan

{"title":"Identification of potential Escherichia coli DNA gyrase B inhibitors targeting antibacterial therapy: an integrated docking and molecular dynamics simulation study.","authors":"Bader S Alotaibi, Mohammed Ageeli Hakami, Talha Jawaid, Nawaf Alshammari, Reem Binsuwaidan, Mohd Adnan","doi":"10.1080/07391102.2023.2249117","DOIUrl":"10.1080/07391102.2023.2249117","url":null,"abstract":"The alarming rise in the rate of antibiotic resistance is a matter of significant concern. DNA gyrase B (GyrB), a critical bacterial enzyme involved in DNA replication, transcription, and recombination, has emerged as a promising target for antibacterial agents. Inhibition of GyrB disrupts bacterial DNA replication, leading to cell death, making it an attractive candidate for antibiotic development. Although several classes of antibiotics targeting GyrB are currently in clinical use, the emergence of antibiotic resistance necessitates the exploration of novel inhibitors. In this study, we aimed to identify potential Escherichia coli GyrB inhibitors from a database of phytoconstituents sourced from Indian medicinal plants. Utilizing virtual screening, we performed a rigorous search to identify compounds with the most promising inhibitory properties against GyrB. Two compounds, namely Zizogenin and Cucurbitacin S, were identified based on their favorable drug likeliness and pharmacokinetic profiles. Employing advanced computational techniques, we analyzed the binding interactions of Zizogenin and Cucurbitacin S with the ATP-binding site of GyrB through molecular docking simulations. Both compounds exhibited robust binding interactions, evidenced by their high docking energy scores. To assess the stability of these interactions, we conducted extensive 100 ns molecular dynamics (MD) simulations, which confirmed the stability of Zizogenin and Cucurbitacin S when bound to GyrB. In conclusion, our study highlights Zizogenin and Cucurbitacin S as promising candidates for potential antibacterial agents targeting GyrB. Experimental validation of these compounds is warranted to further explore their efficacy and potential as novel antibiotics to combat antibiotic-resistant bacteria.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel spice-antioxidant-based nano-vehicle as a putative green alternative of synthetic AChE inhibitor drugs. 一种基于香料抗氧化剂的新型纳米载体，可作为合成 AChE 抑制剂药物的绿色替代品。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-28 DOI: 10.1080/07391102.2023.2248274

Izaz Monir Kamal, Anamika Das, Sanjukta Datta, Kaninika Paul, Sasanka Chakrabarti, Saikat Chakrabarti, Paramita Bhattacharjee

{"title":"A Novel spice-antioxidant-based nano-vehicle as a putative green alternative of synthetic AChE inhibitor drugs.","authors":"Izaz Monir Kamal, Anamika Das, Sanjukta Datta, Kaninika Paul, Sasanka Chakrabarti, Saikat Chakrabarti, Paramita Bhattacharjee","doi":"10.1080/07391102.2023.2248274","DOIUrl":"10.1080/07391102.2023.2248274","url":null,"abstract":"The present treatment for Alzheimer's disease (AD) involves well known synthetic acetylcholine esterase (AChE) inhibitor drugs which besides having short duration of action also have deleterious impact on human health. Therefore, there is a need for natural plant-based biomolecule(s) with potential AChE inhibition activity (ies). The aim of the work is to design a spice-based nano-vehicle as a novel green alternative of synthetic AD drugs by nanoencapsulating a solvent-less supercritical CO2 extract of small cardamom seeds (SCE) having a synergistic consortium of five antioxidant molecules, using polyethylene glycol and emulsifiers, selected based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analyses. Ellman's assay and enzyme inhibition kinetics of the antioxidant molecules as well as the extract and its nanoliposomal formulation (SCE-NL) were performed, followed by rigorous molecular docking and dynamics studies using MM-PBSA and umbrella sampling. The antioxidants exhibited significant AChE inhibition in vitro, individually with 1, 8-cineole having the least IC50 value of 65.53 ± 0.05 µg/mL. . Although SCE-NL had higher IC50 value (575.67 ± 0.5 µg/mL) vis-à-vis that of rivastigmine (67.52 ± 0.02 µg/mL), it is safer for usage being 'green'.The Lineweaver-Burk plots (Vmax ∼1.04 mM/min) revealed competitive mode(s) of inhibition of AChE with each of these antioxidants. Binding energy analyses suggested very good binding free energies and stable docking/binding complexes (between the antioxidants and AChE). This study has delivered a nanoliposomal vehicle of food antioxidants as a putative 'green' alternative of synthetic AChE inhibitor drugs.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Three-helix bundle and SH3-type barrels: autonomously stable structural motifs in small and large proteins. 三螺旋束和 SH3 型桶：小型和大型蛋白质中自主稳定的结构主题。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-28 DOI: 10.1080/07391102.2023.2250450

Kirill Sergeevich Nikolsky, Liudmila Ivanovna Kulikova, Denis Vitalievich Petrovskiy, Vladimir Removich Rudnev, Tatiana Vladimirovna Butkova, Kristina Akhmedovna Malsagova, Arthur Tigranovich Kopylov, Anna Leonidovna Kaysheva

{"title":"Three-helix bundle and SH3-type barrels: autonomously stable structural motifs in small and large proteins.","authors":"Kirill Sergeevich Nikolsky, Liudmila Ivanovna Kulikova, Denis Vitalievich Petrovskiy, Vladimir Removich Rudnev, Tatiana Vladimirovna Butkova, Kristina Akhmedovna Malsagova, Arthur Tigranovich Kopylov, Anna Leonidovna Kaysheva","doi":"10.1080/07391102.2023.2250450","DOIUrl":"10.1080/07391102.2023.2250450","url":null,"abstract":"In this study, we investigated two variants of a three-helix bundle and SH3-type barrel, compact in space, present in small and large proteins of various living organisms. Using a neural graph network, proteins with three-helix bundle (n = 1377) and SH3-type barrels (n = 1914) spatial folds were selected. Molecular experiments were performed for small proteins with these folds, and motifs were studied autonomously outside the protein environment at 300, 340, and 370 K. A comparative analysis of the main parameters of the structures in the course of the experiment was performed, including gyration radius, area accessible to the solvent, number of hydrophobic and hydrogen bonds, and root-mean-square deviation of atomic positions (RMSD). We exhibited an autonomous stability of the studied folds outside the protein environment in an aquatic medium. We aimed to demonstrate the possibility of analyzing three-helix bundle and SH3-type barrels autonomously outside the protein globule, thereby reducing the computational time and increasing performance without significant loss of information.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10102249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sanggenol B, a plant bioactive, as a safer alternative to tackle cancer by antagonising human FGFR. Sanggenol B 是一种植物生物活性物质，可通过拮抗人类表皮生长因子受体（FGFR）作为一种更安全的癌症治疗替代品。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2024-10-01 Epub Date: 2023-08-08 DOI: 10.1080/07391102.2023.2245047

Achyuta Nagaraj, Sriram Srinivasa Raghavan, Ayyadurai Niraikulam, Namasivayam Gautham, Krishnasamy Gunasekaran

{"title":"Sanggenol B, a plant bioactive, as a safer alternative to tackle cancer by antagonising human FGFR.","authors":"Achyuta Nagaraj, Sriram Srinivasa Raghavan, Ayyadurai Niraikulam, Namasivayam Gautham, Krishnasamy Gunasekaran","doi":"10.1080/07391102.2023.2245047","DOIUrl":"10.1080/07391102.2023.2245047","url":null,"abstract":"Fibroblast Growth Receptor Factor (FGFR) are a family of proteins which are, in addition to their biological role, are involved in various pathological functions, such as cancer cellular proliferation, and metastasis. Deregulation of FGFRs at various points could result in malignancy. A conformational transition of the DFG (Asp-Phe-Gly) motif can switch the enzyme from a catalytically active (DFG-in) to an inactive (DFG-out) state. There are a few FDFR inhibitors which have received approval from the FDA, but these have adverse side effects. Hence, there is a demand for safer alternatives. With this aim, Ligand and Structure based virtual screening was carried to identify suitable lead molecule. In this process, Four Featured atom-based 3D Pharmacophore with quantitative structure-activity relationship analysis (3D-QSAR) was developed. The External validation of the hypothesis was carried invoking criteria such as Area under the ROC curve. Natural plant compound databases such as the Traditional Chinese medicine, NPACT and the ZINC Natural databases were chosen for pharmacophore filtering, which was followed by virtual screening against FGFR isoforms. The compound Sanggenol B was identified as the most suitable lead molecule. Structural stability of the protein-ligand complex and interactions of the ligand (Sanggenol B & the reference compound Ponatinib) with FGFR were analysed for 1000 ns (triplicate) by means of molecular simulation and the binding free energy was calculated using MMGBSA. Sanggenol B (PubChem CID: 15233694) binds effectively at the active site with favourable energies and is proposed as a safe alternative from a natural source.Communicated by Ramaswamy H. Sarma.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9956887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0